Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

NOT YET RECRUITING

NCT07577986

PHASE1/PHASE2

A Safety and Efficacy Trial of Chidamide Combined With NKG2D CAR-NK Cell Therapy for Reducing the HIV Viral Reservoir

Sponsor: First Affiliated Hospital of Zhejiang University

View on ClinicalTrials.gov

Summary

This study aims to investigate the safety and preliminary efficacy of an innovative therapeutic strategy combining chidamide with NKG2D-directed chimeric antigen receptor natural killer (CAR-NK) cells in individuals living with HIV. The approach is predicated on the "shock and kill" paradigm: chidamide is employed to reactivate latent HIV reservoirs and upregulate surface target ligands (NKG2D ligands) on infected cells; subsequently, allogeneic NKG2D CAR-NK cells are infused to specifically recognize and eliminate these "marked" cells. This is a phase I, open-label, single-arm clinical trial comprising two distinct stages: a dose-escalation phase (phase Ia, utilizing a "1+3+3" design) and a dose-expansion phase (phase Ib). A total of 20 HIV-infected individuals who are stable on antiretroviral therapy (ART) and have suppressed plasma viremia are planned for enrollment. Participants will receive oral chidamide over approximately five weeks, followed by two cycles of intravenous CAR-NK cell infusion. The primary endpoint is the safety and tolerability of the regimen, with particular attention to immune-related adverse events including cytokine release syndrome (CRS). Secondary endpoints encompass exploratory assessments of potential virologic and immunologic effects, such as alterations in plasma HIV RNA, cell-associated viral nucleic acids, and CD4+ T-cell counts. This study is intended to provide initial human safety data and preliminary evidence regarding the potential of this combination strategy to contribute toward a functional cure for HIV infection.

Key Details

Gender

All

Age Range

18 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-05-01

Completion Date

2027-12-30

Last Updated

2026-05-11

Healthy Volunteers

Conditions

HIV (Human Immunodeficiency Virus)

Interventions

DRUG

Chidamide Combined with NKG2D CAR-NK Cell Therapy

All enrolled participants will receive oral chidamide (10 mg twice weekly) for approximately five weeks. During this period, participants will receive two cycles of intravenous infusion of allogeneic NKG2D CAR-NK cells (each cycle consisting of two consecutive daily infusions, separated by an interval of approximately two weeks). Throughout the treatment course, participants will continue their pre-existing antiretroviral regimen without modification.

Inclusion Criteria A participant will be deemed eligible for enrollment only if all of the following criteria are met: 1. Diagnosis of HIV infection, with a current history of highly active antiretroviral therapy (HAART) for a minimum duration of two years. 2. Age between 18 and 65 years, inclusive. 3. Plasma HIV RNA level \< 50 copies/mL (virologic suppression). 4. CD4⁺ T cell count \> 200 cells/μL. 5. Adequate hematologic function defined as: * Hemoglobin ≥ 90 g/L; * Platelet count ≥ 75 × 10⁹/L; * Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; * White blood cell count ≥ 2 × 10⁹/L. 6. Adequate hepatic and renal function defined as: * Serum creatinine ≤ 1.5 × upper limit of normal (ULN); * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN; * Total bilirubin ≤ 2 × ULN; * Prothrombin time (PT) prolongation \< 3 seconds. 7. Hemodynamically stable with a left ventricular ejection fraction (LVEF) ≥ 45%. 8. Negative serum or urine pregnancy test for females of childbearing potential. 9. Willingness of the participant to: * Practice effective contraception during the study period and for one year following completion of the trial; * Voluntarily provide written informed consent and comply with scheduled follow up visits and study procedures. Exclusion Criteria Participants meeting any of the following criteria will be excluded from study participation: 1. Presence of severe cardiovascular, respiratory, or hematologic disease; active infectious disease (other than controlled HIV infection); or active malignancy. 2. Positive serology for hepatitis B surface antigen (HBsAg) or detectable hepatitis C virus RNA (HCV RNA). 3. Diagnosis of chronic kidney disease (CKD). 4. History or presence of acute or chronic pancreatitis. 5. Active severe peptic ulcer disease. 6. Current severe neurologic or psychiatric disorder. 7. History of alcohol abuse or illicit substance use disorder. 8. Known allergic diathesis or hypersensitivity to any component of the investigational agents. 9. Female participants who are pregnant, lactating, or of childbearing potential and unwilling to adhere to required contraceptive measures. 10. Concurrent use of immunosuppressive agents. 11. Any other condition that, in the opinion of the investigator, renders the participant unsuitable for study participation.

Locations (1)

the first affiliated hospital of Zhejiang university school of medicine, Hangzhou, Zhejiang 310000

Hangzhou, Zhejiang, China